Primary:- Can carboplatin exposure in children be predicted by taking the plasma concentrations of creatinine of cystatine C into account?Secundary:- Which is the effective carboplatin exposure in the current pediatric treatment protocols?- Is there…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Using the NONMEM software (version VI level 1.1, GloboMax LLC, Hanover, MD) a
on-linear mixed-effect population pharmacokinetic model will be calculated
[10]. In this model the concentration of free platina in plasma will be used as
a measure of the plasma carboplatin concentration. Both interindividual (IIV)
and interoccasion variability (IOV) will be modelled.
At least three different models for the description of the relationship between
carboplatin clearance, plasma creatinine and cystatine C will be tested:
The hypothesis that there is not relationship between carboplatin clearance and
the concentration of the kidney function paramers will be used as reference.
This will be compared with models including plasma cystatine C or creatinine or
both. The area-under-the-concentration-time-curve (AUC) as a measure of
effective carboplatin exposure will be calculated from carboplatin clearance
and dose.
Secondary outcome
- Assessment of effective carboplatin exposure in current pediatric treatment
protocols.
- Relationship between effective carboplatin exposure and therapy-related
complications, which will be assessed using the standard procedures of the
individual treatment protocol (blood count, plasma creatinine and cystatin C,
audiometry)
- Relationship between effective carboplatin exposure and DNA-adducts as
measure of carboplatin action on a cellular level.
Background summary
Carboplatin is a toxic cytostatic drug which is mainly excreted by the kidneys.
Previous studies have shown that carboplatin dosage can be optimized if kidney
function is taken into account. In these studies, renal function was measured
using 51Cr-EDTA clearance, which is invasive (radiation risk), costly, time
consuming and not available in many institutions. Recently, endogenous markers
of kidney function (creatinine en cystatin C) have been shown to be useful for
carboplatin dose adjustment in adults.
Study objective
Primary:
- Can carboplatin exposure in children be predicted by taking the plasma
concentrations of creatinine of cystatine C into account?
Secundary:
- Which is the effective carboplatin exposure in the current pediatric
treatment protocols?
- Is there a relationship between effective carboplatin exposure and side
effects?
- Is there a relationship between effective carboplatin exposure and the amount
of DNA-adducts as a measure of carboplatin action on a cellular level?
Study design
Longitudinal observational study as a pilot study.
Measurement of carboplatin concentrations for the calculation of carboplatin
clearance. Analysis of factors which affect carboplatin clearance, namely
endogenous markers of renal function (creatinine and cystatin C).
Study burden and risks
This is an observational study incorporating a low to negligible risk.
Blood will be taken from a central venous line using a Bionecteur® system,
which will further decrease the risk of infectious complications. The amout of
blood taken is minimal and will be limited to 9 ml with a minimum patient
weight of 2.5 kg (i.e. maximum loss of 4.5% of effective blood volume).
As pharmacokinetic data from adults cannot be extrapolated to children, this
study can only be performed in a pediatric population. We expect that the
safety of carboplatin therapy can be improved based on the findings obtained in
this pilot study.
de Boelelaan 1117
1081 HV Amsterdam
Nederland
de Boelelaan 1117
1081 HV Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
Carboplatin therapy, weight above 2.5 kg, central venous line for bloodsampling
Exclusion criteria
Weight below 2.5 kg, no central venous access for bloodsampling
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23370.029.08 |